WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200100
CAS#: 497839-62-0
Description: AEE-788 is an orally bioavailable multiple-receptor tyrosine kinase inhibitor. AEE788 inhibits phosphorylation of the tyrosine kinases of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and vascular endothelial growth factor receptor 2 (VEGF2), resulting in receptor inhibition, the inhibition of cellular proliferation, and induction of tumor cell and tumor-associated endothelial cell apoptosis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).
MedKoo Cat#: 200100
Name: AEE-788
CAS#: 497839-62-0
Chemical Formula: C27H32N6
Exact Mass: 440.26885
Molecular Weight: 440.58
Elemental Analysis: C, 73.60; H, 7.32; N, 19.07
Synonym: AEE788; AEE 788; AEE-788.
IUPAC/Chemical Name: (R)-6-(4-((4-ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine.
InChi Key: OONFNUWBHFSNBT-HXUWFJFHSA-N
InChi Code: InChI=1S/C27H32N6/c1-3-32-13-15-33(16-14-32)18-21-9-11-23(12-10-21)25-17-24-26(28-19-29-27(24)31-25)30-20(2)22-7-5-4-6-8-22/h4-12,17,19-20H,3,13-16,18H2,1-2H3,(H2,28,29,30,31)/t20-/m1/s1
SMILES Code: C[C@@H](NC1=C2C(NC(C3=CC=C(CN4CCN(CC)CC4)C=C3)=C2)=NC=N1)C5=CC=CC=C5
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | AEE788 is an inhibitor of the EGFR and ErbB2 with IC50 values of 2 and 6 nM, respectively. |
| In vitro activity: | This study analyzed the ability of AEE788 to induce apoptosis using Annexin-V and propidium iodide by flow cytometric analysis. THP-1, MOLM-13, and MV4-11 cell lines were treated in vitro with different concentrations of AEE788 for 48 hours. AEE788 induced apoptosis of the AML cells in a dose-dependent manner (Fig. 1A). An apoptosis response of 50% was induced at a concentration of 10 μM for MOLM-13 and MV4-11, and of 15 μM for THP-1 cells. Reference: Exp Hematol. 2010 Aug;38(8):641-52. https://pubmed.ncbi.nlm.nih.gov/20380868/ |
| In vivo activity: | This study compared the antitumor activity of AEE788 against Daoy, DaoyPt, DaoyHER2, and DaoyV xenografts. AEE788 caused a statistically significant reduction in tumor volume of Daoy and DaoyPt xenografts, with a TVI of 51% and 45%, respectively (Figure 4, A and B). DaoyV xenografts behaved as Daoy (data not shown). On the DaoyHER2 xenografts, AEE788 induced a more pronounced tumor inhibition (TVI = 72%; Figure 4C). All the mice survived until the end of the 4-week treatment period, with a less than 15% body weight loss at worst, which was partially recovered by the end of the experiment (Figure 4, D–F). Reference: Transl Oncol. 2010 Oct; 3(5): 326–335. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935636/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 51.77 | 117.5 | |
| DMSO:PBS (pH 7.2) (1:3) | 0.25 | 0.57 | |
| DMF | 25.0 | 56.74 | |
| Ethanol | 5.0 | 11.35 |
The following data is based on the product molecular weight 440.58 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Barbarroja N, Torres LA, Rodriguez-Ariza A, Valverde-Estepa A, Lopez-Sanchez LM, Ruiz-Limon P, Perez-Sanchez C, Carretero RM, Velasco F, López-Pedrera C. AEE788 is a vascular endothelial growth factor receptor tyrosine kinase inhibitor with antiproliferative and proapoptotic effects in acute myeloid leukemia. Exp Hematol. 2010 Aug;38(8):641-52. doi: 10.1016/j.exphem.2010.03.017. Epub 2010 Apr 7. PMID: 20380868. 2. Venkatesan P, Das S, Krishnan MM, Chakraborty C, Chaudhury K, Mandal M. Effect of AEE788 and/or Celecoxib on colon cancer cell morphology using advanced microscopic techniques. Micron. 2010 Apr;41(3):247-56. doi: 10.1016/j.micron.2009.10.008. Epub 2009 Nov 10. PMID: 19945288. 3. Meco D, Servidei T, Zannoni GF, Martinelli E, Prisco MG, de Waure C, Riccardi R. Dual Inhibitor AEE788 Reduces Tumor Growth in Preclinical Models of Medulloblastoma. Transl Oncol. 2010 Oct 1;3(5):326-35. doi: 10.1593/tlo.10163. PMID: 20885895; PMCID: PMC2935636. 4. Deng M, Huang H, Jin H, Dirsch O, Dahmen U. The anti-proliferative side effects of AEE788, a tyrosine kinase inhibitor blocking both EGF- and VEGF-receptor, are liver-size-dependent after partial hepatectomy in rats. Invest New Drugs. 2011 Aug;29(4):593-606. doi: 10.1007/s10637-010-9394-6. Epub 2010 Feb 12. PMID: 20148349. |
| In vitro protocol: | 1. Barbarroja N, Torres LA, Rodriguez-Ariza A, Valverde-Estepa A, Lopez-Sanchez LM, Ruiz-Limon P, Perez-Sanchez C, Carretero RM, Velasco F, López-Pedrera C. AEE788 is a vascular endothelial growth factor receptor tyrosine kinase inhibitor with antiproliferative and proapoptotic effects in acute myeloid leukemia. Exp Hematol. 2010 Aug;38(8):641-52. doi: 10.1016/j.exphem.2010.03.017. Epub 2010 Apr 7. PMID: 20380868. 2. Venkatesan P, Das S, Krishnan MM, Chakraborty C, Chaudhury K, Mandal M. Effect of AEE788 and/or Celecoxib on colon cancer cell morphology using advanced microscopic techniques. Micron. 2010 Apr;41(3):247-56. doi: 10.1016/j.micron.2009.10.008. Epub 2009 Nov 10. PMID: 19945288. |
| In vivo protocol: | 1. Meco D, Servidei T, Zannoni GF, Martinelli E, Prisco MG, de Waure C, Riccardi R. Dual Inhibitor AEE788 Reduces Tumor Growth in Preclinical Models of Medulloblastoma. Transl Oncol. 2010 Oct 1;3(5):326-35. doi: 10.1593/tlo.10163. PMID: 20885895; PMCID: PMC2935636. 2. Deng M, Huang H, Jin H, Dirsch O, Dahmen U. The anti-proliferative side effects of AEE788, a tyrosine kinase inhibitor blocking both EGF- and VEGF-receptor, are liver-size-dependent after partial hepatectomy in rats. Invest New Drugs. 2011 Aug;29(4):593-606. doi: 10.1007/s10637-010-9394-6. Epub 2010 Feb 12. PMID: 20148349. |
1: Behera R, Thomas SM, Mensa-Wilmot K. New chemical scaffolds for human african trypanosomiasis lead discovery from a screen of tyrosine kinase inhibitor drugs. Antimicrob Agents Chemother. 2014;58(4):2202-10. doi: 10.1128/AAC.01691-13. Epub 2014 Jan 27. PubMed PMID: 24468788; PubMed Central PMCID: PMC4023774.
2: Ren J, Bollu LR, Su F, Gao G, Xu L, Huang WC, Hung MC, Weihua Z. EGFR-SGLT1 interaction does not respond to EGFR modulators, but inhibition of SGLT1 sensitizes prostate cancer cells to EGFR tyrosine kinase inhibitors. Prostate. 2013 Sep;73(13):1453-61. doi: 10.1002/pros.22692. Epub 2013 Jun 14. PubMed PMID: 23765757.
3: Katiyar S, Kufareva I, Behera R, Thomas SM, Ogata Y, Pollastri M, Abagyan R, Mensa-Wilmot K. Lapatinib-binding protein kinases in the African trypanosome: identification of cellular targets for kinase-directed chemical scaffolds. PLoS One. 2013;8(2):e56150. doi: 10.1371/journal.pone.0056150. Epub 2013 Feb 20. Erratum in: PLoS One. 2014;9(3):e92488. PubMed PMID: 23437089; PubMed Central PMCID: PMC3577790.
4: Issa A, Gill JW, Heideman MR, Sahin O, Wiemann S, Dey JH, Hynes NE. Combinatorial targeting of FGF and ErbB receptors blocks growth and metastatic spread of breast cancer models. Breast Cancer Res. 2013 Jan 23;15(1):R8. doi: 10.1186/bcr3379. PubMed PMID: 23343422; PubMed Central PMCID: PMC3672810.
5: Baselga J, Mita AC, Schöffski P, Dumez H, Rojo F, Tabernero J, DiLea C, Mietlowski W, Low C, Huang J, Dugan M, Parker K, Walk E, van Oosterom A, Martinelli E, Takimoto CH. Using pharmacokinetic and pharmacodynamic data in early decision making regarding drug development: a phase I clinical trial evaluating tyrosine kinase inhibitor, AEE788. Clin Cancer Res. 2012 Nov 15;18(22):6364-72. doi: 10.1158/1078-0432.CCR-12-1499. Epub 2012 Sep 26. PubMed PMID: 23014528.
6: Venkatesan P, Bhutia SK, Singh AK, Das SK, Dash R, Chaudhury K, Sarkar D, Fisher PB, Mandal M. AEE788 potentiates celecoxib-induced growth inhibition and apoptosis in human colon cancer cells. Life Sci. 2012 Oct 22;91(15-16):789-99. doi: 10.1016/j.lfs.2012.08.024. Epub 2012 Aug 24. PubMed PMID: 22922496.
7: Reardon DA, Conrad CA, Cloughesy T, Prados MD, Friedman HS, Aldape KD, Mischel P, Xia J, DiLea C, Huang J, Mietlowski W, Dugan M, Chen W, Yung WK. Phase I study of AEE788, a novel multitarget inhibitor of ErbB- and VEGF-receptor-family tyrosine kinases, in recurrent glioblastoma patients. Cancer Chemother Pharmacol. 2012 Jun;69(6):1507-18. doi: 10.1007/s00280-012-1854-6. Epub 2012 Mar 7. PubMed PMID: 22392572; PubMed Central PMCID: PMC4351868.
8: Servidei T, Meco D, Trivieri N, Patriarca V, Vellone VG, Zannoni GF, Lamorte G, Pallini R, Riccardi R. Effects of epidermal growth factor receptor blockade on ependymoma stem cells in vitro and in orthotopic mouse models. Int J Cancer. 2012 Sep 1;131(5):E791-803. doi: 10.1002/ijc.27377. Epub 2012 Jan 11. PubMed PMID: 22120695.
9: Reardon DA, Cloughesy T, Rich J, Alfred Yung WK, Yung L, DiLea C, Huang J, Dugan M, Mietlowski W, Maes A, Conrad C. Pharmacokinetic drug interaction between AEE788 and RAD001 causing thrombocytopenia in patients with glioblastoma. Cancer Chemother Pharmacol. 2012 Jan;69(1):281-7. doi: 10.1007/s00280-011-1754-1. Epub 2011 Oct 9. PubMed PMID: 21984222.
10: Wedel S, Hudak L, Seibel JM, Makarević J, Juengel E, Tsaur I, Waaga-Gasser A, Haferkamp A, Blaheta RA. Molecular targeting of prostate cancer cells by a triple drug combination down-regulates integrin driven adhesion processes, delays cell cycle progression and interferes with the cdk-cyclin axis. BMC Cancer. 2011 Aug 25;11:375. doi: 10.1186/1471-2407-11-375. PubMed PMID: 21867506; PubMed Central PMCID: PMC3170298.
AEE788 is a multitargeted human epidermal receptor (HER) 1/2 and vascular endothelial growth factor receptor (VEGFR) 1/2 receptor family tyrosine kinases inhibitor with IC50 of 2, 6, 77, 59 nM for EGFR, ErbB2, KDR, and Flt-1. In cells, growth factor-induced EGFR and ErbB2 phosphorylation was also efficiently inhibited with IC50s of 11 and 220 nM, respectively. It efficiently inhibited growth factor-induced EGFR and ErbB2 phosphorylation in tumors for >72 h, a phenomenon correlating with the antitumor efficacy of intermittent treatment schedules. It also inhibits VEGF-induced angiogenesis in a murine implant model. It has potential as an anticancer agent targeting deregulated tumor cell proliferation as well as angiogenic parameters. (http://en.wikipedia.org/wiki/AEE788)
AEE788 is a multitargeted human epidermal receptor (HER) 1/2 and vascular endothelial growth factor receptor (VEGFR) 1/2 receptor family tyrosine kinases inhibitor with IC50 of 2, 6, 77, 59 nM for EGFR, ErbB2, KDR, and Flt-1. In cells, growth factor-induced EGFR and ErbB2 phosphorylation was also efficiently inhibited with IC50s of 11 and 220 nM, respectively. It efficiently inhibited growth factor-induced EGFR and ErbB2 phosphorylation in tumors for >72 h, a phenomenon correlating with the antitumor efficacy of intermittent treatment schedules. It also inhibits VEGF-induced angiogenesis in a murine implant model. It has potential as an anticancer agent targeting deregulated tumor cell proliferation as well as angiogenic parameters. (http://en.wikipedia.org/wiki/AEE788)
